Active and poised promoter states drive folding of the extended HoxB locus in mouse embryonic stem cells

被引：69

作者：

Barbieri, Mariano ^{[1
,2
,3
,4
]}

Xie, Sheila Q. ^{[5
,6
,7
]}

Triglia, Elena Torlai ^{[1
]}

Chiariello, Andrea M. ^{[2
,3
]}

Bianco, Simona ^{[2
,3
]}

de Santiago, Ines ^{[5
]}

Branco, Miguel R. ^{[5
]}

Rueda, David ^{[6
,7
]}

Nicodemi, Mario ^{[2
,3
,4
]}

Pombo, Ana ^{[1
,4
,5
,8
]}

机构：

[1] Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Epigenet Regulat & Chromatin Architecture Grp, Berlin, Germany

[2] Univ Naples Federico II, Dipartimento Fis, Naples, Italy

[3] Complesso Univ Monte St Angelo, INFN Napoli, Naples, Italy

[4] BIH, Berlin, Germany

[5] Imperial Coll London, MRC London Inst Med Sci LMS, Genome Funct Grp, Hammersmith Hosp Campus, London, England

[6] Imperial Coll London, MRC London Inst Med Sci LMS, Single Mol Imaging Grp, Hammersmith Hosp Campus, London, England

[7] Imperial Coll London, Dept Med, Sect Virol, Hammersmith Hosp Campus, London, England

[8] Humboldt Univ, Inst Biol, Berlin, Germany

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2017年 / 24卷 / 06期

基金：

英国医学研究理事会;

关键词：

RNA-POLYMERASE-II; TRANSCRIPTION FACTORIES; ES CELLS; SPATIAL-ORGANIZATION; HUMAN GENOME; HUMAN NUCLEI; HISTONE H1; IN-VIVO; CHROMATIN; CTCF;

D O I：

10.1038/nsmb.3402

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Gene expression states influence the 3D conformation of the genome through poorly understood mechanisms. Here, we investigate the conformation of the murine HoxB locus, a gene-dense genomic region containing closely spaced genes with distinct activation states in mouse embryonic stem (ES) cells. To predict possible folding scenarios, we performed computer simulations of polymer models informed with different chromatin occupancy features that define promoter activation states or binding sites for the transcription factor CTCF. Single-cell imaging of the locus folding was performed to test model predictions. While CTCF occupancy alone fails to predict the in vivo folding at genomic length scale of 10 kb, we found that homotypic interactions between active and Polycomb-repressed promoters co-occurring in the same DNA fiber fully explain the HoxB folding patterns imaged in single cells. We identify state-dependent promoter interactions as major drivers of chromatin folding in gene-dense regions.

引用

页码：515 / +

页数：13

共 65 条

[1] Polycomb complexes in stem cells and embryonic development [J].